Pattern of colorectal surgery and long-term survival:10-year experience from a single center

BACKGROUND The incidence of colorectal cancer(CRC)has increased in recent decades,and ranks fourth among males and third among females in China.Surgical resection remains the most important treatment modality for curative intent in CRC.Several studies found that surgeon volumes and specialization appeared to be associated with improved overall survival(OS).Moreover,numerous reports have suggested that specialization and minimally invasive surgery have gained increased popularity in CRC surgery.However,few studies have specifically examined the role and long-term survival of all stage CRC in a real-world study.AIM To evaluate the effect of surgeon specialization on survival changes and minimally invasive surgery utilization in a real world study.METHODS A retrospective analysis on the association between surgeon specialization and OS between 2008 and 2013 in Zhongshan Hospital CRC database was performed.Standard demographic,clinicopathologic,surgical and follow-up data were obtained from the CRC database.Surgeon specialty was categorized as colorectal surgeon(CS)and general surgeon(GS).CRC patients who underwent primary surgical resection were enrolled.RESULTS A total of 5141 CRC patients who underwent primary surgical resection between 2008 and 2013 were evaluated,1748(34.0%)of these by CS.The percentage of minimally invasive procedures in the CS group showed an increasing trend.There was no benefit associated with surgeon specialization for stage I,II and IV patients.Surgeon specialization exhibited a significant association with OS solely among stage III patients,with 5-year OS rates of 76%and 67%for the CS and GSgroups,respectively(P<0.01).Further analyses found that surgeon specialization was significantly associated with survival only in stage III rectal patients,and the 5-year OS rate in the CS group and GS group was 80%and 67%,respectively(P<0.01).CONCLUSION Surgeon specialization is associated with improved OS after primary surgery in stage III rectal patients.An appropriate surgical technique,perioperative program and adjuvant therapy may contribute to survival benefit in these patients.

High patatin like phospholipase domain containing 8 expression as a biomarker for poor prognosis of colorectal cancer

BACKGROUND Patatin like phospholipase domain containing 8(PNPLA8)has been shown to play a significant role in various cancer entities.Previous studies have focused on its roles as an antioxidant and in lipid peroxidation.However,the role of PNPLA8 in colorectal cancer(CRC)progression is unclear.AIM To explore the prognostic effects of PNPLA8 expression in CRC.METHODS A retrospective cohort containing 751 consecutive CRC patients was enrolled.PNPLA8 expression in tumor samples was evaluated by immunohistochemistry staining and semi-quantitated with immunoreactive scores.CRC patients were divided into high and low PNPLA8 expression groups based on the cut-off va-lues,which were calculated by X-tile software.The prognostic value of PNPLA8 was identified using univariate and multivariate Cox regression analysis.The over-all survival(OS)rates of CRC patients in the study cohort were compared with Kaplan-Meier analysis and Log-rank test.RESULTS PNPLA8 expression was significantly associated with distant metastases in our cohort(P=0.048).CRC patients with high PNPLA8 expression indicated poor OS(median OS=35.3,P=0.005).CRC patients with a higher PNPLA8 expression at either stage I and II or stage III and IV had statistically significant shorter OS.For patients with left-sided colon and rectal cancer,the survival curves of two PN-PLA8-expression groups showed statistically significant differences.Multivariate analysis also confirmed that high PNPLA8 expression was an independent prog-nostic factor for overall survival(hazard ratio HR=1.328,95%CI:1.016-1.734,P=0.038).

Efficacy of image-enhanced endoscopy for colorectal adenoma detection:A multicenter,randomized trial

BACKGROUND Improved adenoma detection at colonoscopy has decreased the risk of developing colorectal cancer.However,whether image-enhanced endoscopy(IEE)further improves the adenoma detection rate(ADR)is controversial.AIM To compare IEE with white-light imaging(WLI)endoscopy for the detection and identification of colorectal adenoma.METHODS This was a multicenter,randomized,controlled trial.Participants were enrolled between September 2019 to April 2021 from 4 hospital in China.Patients were randomly assigned to an IEE group with WLI on entry and IEE on withdrawal(n=2113)or a WLI group with WLI on both entry and withdrawal(n=2098).The primary outcome was the ADR.The secondary endpoints were the polyp detection rate(PDR),adenomas per colonoscopy,adenomas per positive colonoscopy,and factors related to adenoma detection.RESULTS A total of 4211 patients(966 adenomas)were included in the analysis(mean age,56.7 years,47.1%male).There were 2113 patients(508 adenomas)in the IEE group and 2098 patients(458 adenomas)in the WLI group.The ADR in two group were not significantly different[24.0%vs 21.8%,1.10,95%confidence interval(CI):0.99-1.23,P=0.09].The PDR was higher with IEE group(41.7%)than with WLI group(36.1%,1.16,95%CI:1.07-1.25,P=0.01).Differences in mean withdrawal time(7.90±3.42 min vs 7.85±3.47 min,P=0.30)and adenomas per colonoscopy(0.33±0.68 vs 0.28±0.62,P=0.06)were not significant.Subgroup analysis found that with narrowband imaging(NBI),between-group differences in the ADR,were not significant(23.7%vs 21.8%,1.09,95%CI:0.97-1.22,P=0.15),but were greater with linked color imaging(30.9%vs 21.8%,1.42,95%CI:1.04-1.93,P=0.04).the second-generation NBI(2G-NBI)had an advantage of ADR than both WLI and the first-generation NBI(27.0%vs 21.8%,P=0.01;27.0%vs 21.2.0%,P=0.01).CONCLUSION This prospective study confirmed that,among Chinese,IEE didn’t increase the ADR compared with WLI,but 2G-NBI increase the ADR.

Robot-assisted one-stage resection of rectal cancer with liver and lung metastases

The Da Vinci Surgical System may help to overcome some of the difficulties of laparoscopy for complicated abdominal surgery.The authors of this article present a case of robot-assisted, one-stage radical resection of three tumors, including robotic anterior resection for rectal cancer, segmental hepatectomy for liver metastasis, and wedge-shaped excision for lung metastasis.A 59-year-old man with primary rectal cancer and liver and lung metastases was operated upon with a one-stage radical resection approach using the Da Vinci Surgical System.Resection and anastomosis of rectal cancer were performed extracorporeally afterundocking the robot.The procedure was successfully completed in 500 min.No surgical complications occurred during the intervention and postoperative period, and no conversion to laparotomy or additional trocars were required.To the best of our knowledge, this is the first case of simultaneous resection for rectal cancer with liver and lung metastases using the Da Vinci Surgery System to be reported.The procedure is feasible and safe and its main advantages for patient are avoiding repeated operation, reducing surgical trauma, shortening recovery time, and early implementation of postoperative adjuvant therapy.

Self-expandable metallic stent placement plus laparoscopy for acute malignant colorectal obstruction

AIM:To investigate the clinical advantages of the stent-laparoscopy approach to treat colorectal cancer(CRC)patients with acute colorectal obstruction(ACO).METHODS:From April 2008 to April 2012,surgeryrelated parameters,complications,overall survival(OS),and disease-free survival(DFS)of 74 consecutive patients with left-sided CRC presented with ACO who underwent self-expandable metallic stent(SEMS)placement followed by one-stage open(n=58)or laparoscopic resection(n=16)were evaluated retrospectively.The stent-laparoscopy group was also compared with a control group of 96 CRC patients who underwent regular laparoscopy without ACO between January 2010 and December 2011 to explore whether SEMS placement influenced the laparoscopic procedure or reduced long-term survival by influencing CRC oncological characteristics.RESULTS:The characteristics of patients among these groups were comparable.The rate of conversion to open surgery was 12.5%in the stent-laparoscopy group.Bowel function recovery and postoperative hospital stay were significantly shorter(3.3±0.9 d vs 4.2±1.5 d and 6.7±1.1 d vs 9.5±6.7 d,P=0.016 and P=0.005),and surgical time was significantly longer(152.1±44.4 min vs 127.4±38.4 min,P=0.045)in the stent-laparoscopy group than in the stent-open group.Surgery-related complications and the rate of admission to the intensive care unit were lower in the stent-laparoscopy group.There were no significant differences in the interval between stenting and surgery,intraoperative blood loss,OS,and DFS between the two stent groups.Compared with those in the stentlaparoscopy group,all surgery-related parameters,complications,OS,and DFS in the control group were comparable.CONCLUSION:The stent-laparoscopy approach is a feasible,rapid,and minimally invasive option for patients with ACO caused by left-sided CRC and can achieve a favorable long-term prognosis.

Anti-EGFR and anti-VEGF agents:Important targeted therapies of colorectal liver metastases

Colorectal liver metastasis (CLM) is common worldwide. Targeted therapies with monoclonal antibodies have been proven effective in numerous clinical trials, and are now becoming standards for patients with CLM. The development and application of anti-epidermal growth factor receptor (anti-EGFR) and anti-vascular endothelial growth factor (anti-VEGF) antibodies represents significant advances in the treatment of this disease. However, new findings continue to emerge casting doubt on the efficacy of this approach. The Kirsten rat sarcoma viral oncogene (KRAS) has been proven to be a crucial predictor of the success of anti-EGFR treatment in CLM. Whereas a recent study summarized several randomized controlled trials, and showed that patients with the KRAS G13D mutation significantly benefited from the addition of cetuximab in terms of progress-free survival (PFS, 4.0 mo vs 1.9 mo, HR = 0.51, P = 0.004) and overall survival (OS, 7.6 mo vs 5.7 mo, HR = 0.50, P = 0.005). Some other studies also reported that the KRAS G13D mutation might not be absolutely predictive of non-responsiveness to anti-EGFR therapy. At the same time, &#x0201c;new&#x0201d; RAS mutations, including mutations in neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS) and exons 3 and 4 of KRAS, have been suggested to be predictors of a poor treatment response. This finding was first reported by the update of the PRIME trial. The update showed that for patients with non-mutated KRAS exon 2 but other RAS mutations, panitumumab-fluorouracil, leucovorin, and oxaliplatin (FOLFOX)4 treatment led to inferior PFS (HR = 1.28, 95%CI: 0.79-2.07) and OS (HR = 1.29, 95%CI: 0.79-2.10), which was consistent with the findings in patients with KRAS mutations in exon 2. Then, the update of the PEAK trial and the FIRE-III trial also supported this finding, which would reduce candidates for anti-EGFR therapy but enhance the efficacy. In first-line targeted combination therapy, the regimens of cetuximab plus FOLFOX was called into question because of the inferior prognosis in the COIN trial and the NORDIC-VII trial. Also, bevacizumab plus oxaliplatin-based chemotherapy was questioned because of the NO16966 trial. By the update and further analysis of the COIN trial and the NORDIC-VII trial, cetuximab plus FOLFOX was reported to be reliable again. But bevacizumab plus oxaliplatin-based chemotherapy was still controversial. In addition, some trials have reported that bevacizumab is not suitable for conversion therapy. The results of the FIRE-III trial showed that cetuximab led to a significant advantage over bevacizumab in response rate (72% vs 63%, P = 0.017) for evaluable population. With the balanced allocation of second-line treatment, the FIRE-III trial was expected to provide evidence for selecting following regimens after first-line progression. There is still no strong evidence for the efficacy of targeted therapy as a preoperative treatment for resectable CLM or postoperative treatment for resected CLM, although the combined regimen is often administered based on experience. Combination therapy with more than one targeted agent has been proven to provide no benefit, and even was reported to be harmful as first-line treatment by four large clinical trials. However, recent studies reported positive results of erlotinib plus bevacizumab for maintenance treatment. The mechanism of antagonism between different targeted agents deserves further study, and may also provide greater understanding of the development of resistance to targeted agents.

Primary colonic melanoma presenting as ileocecal intussusception: Case report and literature review

Primary malignant melanoma originating in the colon is an extremely rare disease.Herein,we report a case of primary melanoma of the ascending colon.The patient was a 57-year-old male who was admitted to our hospital for persistent abdominal pain and episodes of bloody stool,nausea and vomiting.A computed tomography scan revealed lower intestinal intussusception and enlarged lymph nodes in the abdominal cavity and retroperitoneum.During laparoscopic operation,multiple enlarged lymph nodes were found.Several segments of the proximal small intestine were incarcerated into the distal small intestine,forming an internal hernia and obstruction.The necrotic terminal ileum was invaginated into the ascending cecum.Subsequently,adhesive internal hernia reduction and palliative right hemicolectomy were performed.Pathologic examination of the excised specimen revealed a polypoid mass in the ascending colon.Histological examination showed epithelioid and spindle tumor cells with obvious cytoplasmic melanin deposition.Immunohistochemical staining revealed that the tumor cells were positive for S-100,HmB-45 and vimentin,confirming the diagnosis of melanoma.The patient history and a thorough postoperative investigation excluded the preexistence or coexistence of a primary lesion elsewhere in the skin,anus or oculus or at other sites.Thus,we consider our case to represent an aggressive primary colon melanoma presenting as ileocecal intussusception and intestinal obstruction.

Early activated hepatic stellate cell-derived molecules reverse acute hepatic injury

AIM: To test whether hepatic stellate cells(HSCs) at different activation stages play different roles in acetaminophen(APAP)-induced acute liver injury(ALI).METHODS: HSCs were isolated from mouse liver and cultured in vitro.Morphological changes of initiation HSCs [HSCs(5d)] and perpetuation HSCs [HSCs(p3)] were observed by immunofluorescence and transmission electron microscopy.The protective effects of HSCderived molecules, cell lysates and HSC-conditioned medium(HSC-CM) were tested in vivo by survival and histopathological analyses.Liver injury was determined by measuring aminotransferase levels in the serum and by histologic examination of tissue sections under a light microscope.Additionally, to determine the molecular mediators of the observed protective effects of initiation HSCs, we examined HSC-CM using a highdensity protein array.RESULTS: HSCs(5d) and HSCs(p3) had different morphological and phenotypic traits.HSCs(5d) presented a star-shaped appearance with expressing α-SMA at non-uniform levels between cells.However, HSCs(p3) evolved into myofibroblast-like cells without lipid droplets and expressed a uniform and higher level of α-SMA.HSC-CM(5d), but not HSC-CM(p3), provided a significant survival benefit and showed a dramatic reduction of hepatocellular necrosis and panlobular leukocyte infiltrates in mice exposed to APAP.However, this protective effect was abrogated at higher cell masses, indicating a therapeutic window of effectiveness.Furthermore, the protein array screenrevealed that HSC-CM(5d) was composed of many chemokines and growth factors that correlated with inflammatory inhibition and therapeutic activity.When compared with HSC-CM(p3), higher levels of monocyte chemoattractant protein-1, macrophage inflammatory protein-1γ, hepatocyte growth factor, interleukin-10, and matrix metalloproteinase-2, but lower levels of stem cell factor and Fas-Ligand were observed in HSCCM(5d).CONCLUSION: These data indicated that initiation HSCs and perpetuation HSCs were different in morphology and protein expression, and provided the first experimental evidence of the potential medical value of initiation HSC-derived molecules in the treatment of ALI.

Ocular manifestations of Alport syndrome

AIMTo analyze the clinical manifestation of Alport syndrome, especially the ocular features.